The trafficking of fatty acids into and out of adipocytes is regulated by a complex series of proteins and enzymes and is under control by a variety of hormonal and metabolic factors. The biochemical basis of fatty acid influx, despite its widespread appreciation, remains enigmatic with regard to the biophysical and biochemical properties that facilitate long-chain fatty acid uptake. Fatty acid efflux is initiated by hormonally controlled lipolysis of the droplet stores and produces fatty acids that must transit from their site of production to the plasma membrane and subsequently out of the cells. This review will focus on the “in's and out's” of fatty acid trafficking and summarize the current concepts in the field.